Hexafluoro-1,25-dihydroxyvitamin D3 has markedly increased potency in inhibiting proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin D3

Background Although topical 1,25-dihydroxyvitamin D-3 (calcitriol, 1,25(OH)(2)D-3) and its analogues, calcipotriol and tacalcitol, are effective for patients with psoriasis, some patients show little or no response. There is a need to develop more potent analogues of 1,25(OH)(2)D-3. Hexafluoro-1,25(OH)(2)D-3 (F-6-1,25(OH)(2)D-3) is at least 10 times more potent than 1,25(OH)(2)D-3 on calcium metabolism. Objectives We were interested in whether F-6-1,25(OH)(2)D-3 was also more potent than 1,25(OH)(2)D-3 in inhibiting normal human and psoriatic keratinocyte proliferation. Methods The antiproliferative activity of F-6-1,25(OH)(2)D-3 and 1,25(OH)(2)D-3 was determined by H-3-thymidine incorporation into keratinocyte DNA and by counting basal cells. Results F-6-1,25(OH)(2)D-3 was approximately 10-fold more active and had a longer lasting antiproliferative effect than 1,25(OH)(2)D-3 on normal human keratinocytes, and was about 100-fold more potent than 1,25(OH)(2)D-3 on human psoriatic keratinocytes as determined by H-3-thymidine incorporation. F-6-1,25(OH)(2)D-3 also caused a dose-dependent decrease in the number of basal cells and was 100-fold more active than 1,25(OH)(2)D-3. Conclusions The increased potency and the long-lasting effects of F-6-1,25(OH)(2)D-3 suggest that F-6-1,25(OH)(2)D-3 may be a potent candidate agent for treating psoriasis.